PROJECT SUMMARY/ABSTRACT There is clear evidence of sex-disparity in the maintenance of smoking, such that women compared to men, are more vulnerable to the reinforcing value of cigarettes (i.e., nicotine reinforcement) and are less successful in quitting smoking. Ovarian hormones (estradiol, progesterone) are a biological mechanism that may account for nicotine reinforcement in women. Estradiol appears to enhance nicotine sensitivity, while progesterone decreases its rewarding value. Additionally, lower levels of estradiol and progesterone may increase risk for heighted negative affect and poor emotion regulation. Thus, frequent fluctuations in estradiol and progesterone during the menstrual cycle may contribute to intermittent periods of exacerbated negative affect and somatic distress, and deplete adaptive emotion regulation abilities, which may make women especially vulnerable to nicotine reinforcement. However, existing studies infrequently measure ovarian hormones during a women?s cycle (only 1-4 times), which limits precision in knowledge about fluctuations in ovarian hormones within-cycle as it relates to smoking. Additionally, no studies to date have examined the nature of smoking-ovarian hormones among female smokers with anxiety psychopathology. This is surprising given women are twice as likely to have an anxiety disorder compared to men. Additionally, anxiety disorders are linked to nicotine reinforcement and lower quit success. Two specific anxiety vulnerability factors that have been robustly linked to anxiety-smoking comorbidity are anxiety sensitivity (AS: fear of anxiety and bodily sensations) and distress intolerance (DI: one?s perceived or behavioral incapacity to withstand distress states. For certain women (i.e., elevated AS or DI) there may be specific times during their menstrual cycle when, due to fluctuating E2 and P, they are more vulnerable to nicotine reinforcement. The proposed study is an observational within-subjects test of 72 biologically female smokers (ages 18-40) with a normal menstrual cycle (25-35 days), not altered by hormonal contraceptive. Over the course of a full menstrual cycle, daily saliva samples will be collected to directly assess progesterone and estradiol, and will be paired with daily ecological momentary assessment (EMA) of emotion and nicotine reinforcement reported in ?real-time? from women in their natural environments. The primary aim is to examine daily fluctuations in salivary estradiol and progesterone over the course of a women?s complete menstrual cycle and its effect on daily (a) emotional processes and (b) nicotine reinforcement. The secondary aim is to examine the role moderating role of anxiety vulnerability (AS and DI). An additional exploratory aim is to explore whether emotional processes mediate the link between ovarian hormones and nicotine reinforcement. This study has the potential to improve treatment decision-making for female smokers around their menstrual cycle, including when in their cycle to intervene, what specific type of intervention is needed, and for whom specific intervention is most needed (e.g., women with anxiety vulnerability).